Hydrazine peptide synthesis

The Dmab group was developed for glutamic acid protection during Fmoc/r-Bu based peptide synthesis. The group shows excellent acid stability and stability toward 20% piperidine in DMF. It is formed from the alcohol using the DCC protocol for ester formation and is cleaved with 2% hydrazine in DMF at rt. ... 

When the Ac group is removed (20% piperidine/DMF or 5% hydrazine/DMF), it becomes the Hmb group that is used to improve solubility and prevent aspar-tamide formation and is readily cleaved with TFA. The related 2-Fmoc-4-methoxybenzyl group has also been prepared and used in peptide synthesis. ... 

The polymeric resin used for Merrifield solid-phase peptide synthesis (Section 26.8) is prepared by treating polystyrene with iV-(hydroxymethyl) phthalimide and trifluoromethanesulfonic acid, followed by reaction with hydrazine. Propose a mechanism for both steps. 

The polymer-bound p-nitrobenzophenone oxime (71d) has been found to be a suitable support for stepwise peptide synthesis. Protected peptides can be assembled on 70d by coupling and deprotection steps similar to those employed in the usual Merrifield solid-phase procedures (Scheme 39). Cleavage of peptides from 71d can be accomplished with hydrazine and amino acid esters under mild conditions, which do not affect benzyl ester side-chain protecting groups. 

The addition of hydrazine to diphenylvinylene carbonate 92 quantitatively affords a 1 1 mixture of perhydro-l,3,4-oxadiazin-2-one 93 and 2-oxazolidinone 94 derivatives, both of which are smoothly dehydrated with P2O5 to afford 1,3,4-oxadiazin-2-one 95 and 3-amino-2(3//)-oxazolone 96 (Fig. 5.24), respectively. Addition of primary amines to diphenylvinylene carbonate results in exclusive formation of 3-aIkyl-2(3//)-oxazolones, previously investigated as amino protecting groups in peptide synthesis. 

Support-bound triacylmethanes (e.g. 2-acetyldimedone) readily react with primary aliphatic amines to yield enamines. These are stable towards weak acids and bases, and can be used as linkers for solid-phase peptide synthesis using either the Boc or Fmoc methodologies, as well as for the solid-phase synthesis of oligosaccharides [456]. Cleavage of these enamines can be achieved by treatment with primary amines or hydrazine (Entries 2 and 3, Table 3.23 see also Section 10.1.10.4). 

Reagents. Reagents for peptide synthesis are Va-Fmoc-Lys(Dde)-OH and /Va -Boc-Glu(ODmab)-OH, acetic anhydride, PyBOP, DIEA, l-hydroxy-7-azabenzotriazole (HOAt), and 2% hydrazine/DMF. 

The commercially available oxime linker 1.15 (72) has been used in peptide synthesis and for the SPS of small organic molecules such as indoles. Cleavage is carried out with either hydrazine (0.5 M hydrazine in CHCb-MeOH 2/1 for 10 min at rt) or with aliphatic amines or amino esters (DCM at rt for 12 h) to produce hydrazides and amides, respectively. 

The polymeric resin u cpeptide synthesis 1 Section 26.111 is prepared by treating poty nrene with jV-sulfonic acid, followed by reaction with hydrazine. Projioee a naccha-nism for both steps. 

The ethylaminocarbonyl (ethylcarbamyl, EC) derivatives of N-protected cysteine or cysteine are readily obtained by reaction with ethyl isocyanate under anhydrous conditions (Scheme 18) [231,233] pjjjg S-protection is stable toward acids such as HBr/AcOH or TFA, as well as to the standard conditions of peptide synthesis. Deprotection is achieved by treatment with 1M aqueous sodium hydroxide, hydrazine, or ammonia in methanol,or by exposure to sU-ver(I) or mercury(II) ions.t l... 

Peptide synthesis. Hofmann employed the reagent in a novel scheme for peptid% synthesis illustrated as follows. An N-protected amino acid chloride (1) i.s condensed with the reagent to form a peptide bond (2) and the protective phthuloyl group li removed with hydrazine In liberate the free amino group (3) for coupling with 1... 

In peptide synthesis involving use of the N-protective phthaloyl group, hydrazine is a useful reagent for removal of the protective group. The protected peptide is... 

Peptide synthesis. Hydrazine acetate is an effective reagent for cleaving protective N-phthaloyl groups in a neutral medium and hence can be used in the synthesis of alkali-sensitive peptides such as a-melanotropin. Tlius this substance... 

The Dde group was developed for amine protection in solid-phase peptide synthesis. It is formed from 2-acetyldimedone in DMF and cleaved using 2% hydrazine in DMF or ethanolamine." Hydrazinolysis of the Dde group in the presence of the... 

Protected amino acids and peptides in the form of aminomethylene-dimedone derivatives are formed and cleaved very readily. The cleavage with hydrazine in DMF proceeds at room temperature. This protection method is suitable for solid-phase peptide synthesis. 

Applications of Chemical Ligation in Peptide Synthesis via Acyl Transfer Table 1 Cyclic peptides prepared by hydrazine ligation... 

L.A. Carpino, Oxidative reactions of hydrazine, II. Isophthalimides. New protective groups on nitrogen. J. Amer. Chem. Soc. 79 98-101 (1957) F.C. McKay, N.F. Albertson, New amine-masking groups for peptide synthesis, J. Amer. Chem. Soc. 79 4686-4690 (1957)... 

M-NaOH, or NHg, or hydrazine, opening up the possibilities of peptide synthesis with satisfactory cleavage of the completed peptide from the polystyrene support. ... 

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